迟发性运动障碍的诊疗进展

迟发性运动障碍(TD)典型表现为口舌舞蹈症,也可表现为痉挛性斜颈、其他形式的肌张力障碍、抽动和震颤,由长期服用多巴胺受体阻断剂引起,停用致病药物症状常不能完全消除,甚至有可能加重.本文综述TD的危险因素、临床特征、诊断、鉴别诊断以及治疗.     

迟发性运动障碍的药物治疗进展

本文报告迟发性运动障碍应用维生素Ｅ、氯硝西泮、苯妥英钠、氯氮平、左旋千金藤立定、硝苯地平、泰必利、丁螺环酮诸药的治疗进展。     

氯氮平致迟发性肌张力障碍伴迟发性运动障碍

陈某 ,男 ,4 2岁 ,农民 ,未婚 ,住院号 :930 0 2 0 ,无特殊原因起病 ,逐步懒散 ,自言自语 ,无故发笑 ,疑人迫害 ,行为紊乱 3年 ,于 1999年 1月入院 ,无阳性家庭史 ,躯体及神经系统体检 (一 ) ,诊断精神症未定型。氯氮平 1日 10 0 mg递增30 0 mg治疗 ,逐步好转 ,3个月后减量至 1日 2 0 0 mg,5月初出现头颈向左歪斜 ,胸锁乳突肌紧张性增高 ,呈痉挛性斜颈 ,伴有频频不自主咀嚼动作 ,颈背微向前倾 ,有疼痛感 ,进食时有所缓解 ,睡眠时明显缓解 ,情绪激动时加剧。在谈论要娶亲时高兴得头更歪了 ,拟氯氮所致 ,遂改用舒必利 ,然症状改善不明显 ,持至…     

丁螺环酮治疗迟发性运动障碍

观察丁螺环酮治疗迟发性运动障碍的疗效。方法：ＴＤ病人３２例（男性２５例，女性７例，年龄３６±ｓ９ａ），剂量按递增法口服给药，丁螺环酮为１０￣１５０ｍｇ／ｄ，治疗８ｗｋ。结果：ＴＤ症状消失１９例，减轻７例，无效６例（１９％），临床总有效率为８１％，未出现丁螺环酮所致严重副作用。结论：丁螺环酮是一种较好的治疗ＴＤ的药物。     

维生素E治疗迟发性运动障碍

观察维生素Ｅ治疗迟发性运动障碍的疗效。方法：２１例病人（男性１８例，女性３例；年龄４０±ｓ１２ａ），给予维生素Ｅ（１．２ｇ／ｄ）和安慰剂进行为期２２ｗｋ的双盲自身交叉对照研究。结果：维生素Ｅ对迟发性运动障碍的疗效优行安慰剂，Ｐ〈０．０１，而且婷发性运动障碍发生时间愈短疗效愈好。结论：维生素Ｅ治疗迟发性运动障碍有效，且病程愈程效果愈好。     

千金藤立定治疗迟发性运动障碍30例

在原有抗精神病药治疗情况下,合用-千金藤立定(SPD)治疗迟发性运动障碍(TD)30例。SPD剂量50mg tid,一个疗程8wk。结果显效率23％,总有效率56％;大多数4wk内生效,亦有8wk才生效。SPD无明显副作用,未增多或加重抗精神病药副作用,精神病症状也未恶化。初步认为SPD治疗TD安全有效。     

迟发性运动障碍流行病学研究概况

由酚噻嗪类或萝夫木类药所致的锥外神经系统合并症,特别是停止使用抗精神病药物时也不消失的帕金森氏症,首先于本世纪50年代由Schonecker描述。1959年,Sigward将此综合症称为“颊-舌-咀嚼运动异常”,并指出长期使用抗精神病药是产生该综合症的原因。1965年,Druckman将这一综合症称为“迟发性运动异常”。70年代,该综合症统称为迟发性运动障碍(tardive dyskinesia,     

含有甲氧氯普胺的药品易致迟发性运动障碍

美国FDA最近要求所有含甲氧氯普胺（胃复安）的药品生产厂商在其产品标签上增加一条更为醒目的“黑框”警告,以警示长期使用这类药物易致迟发性运动障碍。 迟发性运动障碍的特征是肢体非自主地反复运动,或伴有咂嘴、扮鬼脸、吐舌、快眼运动或眨眼、嘴唇起皱或手指僵硬,这些症状通常不可逆且尚无药可治。不过,有些患者在停药后症状减轻。     

舒必利致迟发性运动障碍

1例34岁男性精神病患者,给予舒必利100mg,2次/d。4周后患者出现不自主吐舌,伴流涎。立即停用舒必利,给予东莨菪碱及地西泮。3h后症状缓解,3d后症状消失。随后改用奥氮平控制精神病。随访2个月余无复发。     

碳酸锂治疗迟发性运动障碍2例

迟发性运动障碍（tardivedyskinesia,TD陈长期服用抗精神病药物引起的特殊而持久的锥体外系反应,其主要表现为不自主动作．在长期服药的精神病病人中发生率为14W15％,而且处理较困难,近年来受到较多关注．TD的发生机理尚不清楚,多数研究者认为是由于脑黑质一纹状体多巴胶功能相对增高所致【'］．过去许多学者曾试用过多种药物,但疗效均不肯定,我们成功地用碳酸理治疗2例TD患者,现报道如下．2例均为男患,同为41岁,工人,有长期精神病史,依据CCMD－2－R分别诊断为精神分裂症及酒精所致精神障碍．人院后出现TD症状：不自主咀…     

Valbenazine for the treatment of tardive dyskinesia

Introduction: Tardive dyskinesia (TD) is a hyperkinetic movement disorder that may result from treatment with antipsychotics or other dopamine receptor blocking agents. Underlying pathophysiology is incompletely understood but since the 1970s dopamine depleting agents have been used to reduce involuntary movements. The search for safe, effective treatments for TD is ongoing. Valbenazine, a novel VMAT2 inhibitor, has recently been FDA approved for treatment of TD.

Areas covered: An overview of TD, unmet medical needs and current treatment guidelines are presented. The background, chemistry and clinical development of valbenazine to treat TD is detailed. A competitive market is developing as the treatment gap is identified and potential therapies are discussed in context of a broader market overview.

Expert opinion: Antipsychotic use is growing among adults and children in the U.S. Consequently, prevalence of TD is expected to rise. Cessation of antipsychotics is often not possible as the psychiatric condition may deteriorate. Increasing doses of an antipsychotic to suppress involuntary movements is not sustainable long term as underlying TD worsens and movements typically recur. There were no FDA approved treatments for TD. The approval of valbenazine to treat TD is a critical step in addressing this gap in neurologic care.     

Valbenazine granted breakthrough drug status for treating tardive dyskinesia

The chronic use and high dosing of typical neuroleptics or centrally acting dopamine receptor blocking antiemetics predispose patients to the onset of tardive syndromes. One particular subtype, tardive dyskinesia, is characterized by rapid, repetitive, stereotypic, involuntary movements of the face, limbs or trunk. The inhibition of the vesicular monoamine transporter system, using tetrabenazine therapy, improves the severity of tardive dyskinesia. But there are also drawbacks to tetrabenazine treatment, such as a fluctuating response and the need for frequent intake due to its rapid metabolism. Clinical research on the potentially more efficacious and easier to use tetrabenazine analogs is already under way. One of them is valbenazine, the purified parent drug of the (+)-α-isomer of tetrabenazine. The FDA lowered approval hurdles for valbenazine due to a successful Phase II trial, which showed a distinctive improvement in tardive dyskinesia symptoms during valbenazine administration. This resurgence in the clinical research of tardive syndrome therapy is most welcome. This author notes that the putative long-term side effects of valbenazine should carefully be investigated in the future via naturalistic observational trials. Furthermore, valbenazine may also support the onset of symptoms, such as Parkinsonism and depression, with chronic administration, as it, to a certain extent, shares the mode of action of tetrabenazine.     

Targeted to medication-induced dyskinesia and tardive dyskinesia:A role of 5-HT_(1A) receptor

Objective To outline the recent progress in drug discovery for medication-induced dyskinesia(Parkinson disease,PD)and tardive diskinesia(schizophrenia)with emphasizing the role of 5-HT1A receptor.Methods Development of extrapyramidal syndrome(EPS)followed either chronic L-DOPA administration in PD(L-DOPA-induced dyskinesia,LID)or antipsychotic treatment in schizophrenia(Tardive dyskinesia,TD)remains a challenge in the clinical practice and drug discovery.In addition to the abnormal dopamine activity in the nigrostrial area that contributes to the LID or TD,recent information indicates that 5-HT1A receptor also plays an important role which is merging as promising target in treatment of LID or TD.Results l-Stepholidine(l-SPD),isolated from the Chinese herb Stephania,is known as a dual dopamine receptor agent(D1 receptor agonistic and D2 antagonistic activity).In addition,we further demonstrated that l-SPD binds to 5-HT1A receptor and exhibits a partial agonistic activity.In LID rat model,l-SPD not only attenuated the development of L-DOPA-induced dyskinesia(LID),but also relived the established LID.The effect of l-SPD on LID was completely blocked by pretreatment of 5-HT1A receptor antagonist,indicating the role of 5-HT1A receptor.Furthermore,we designed and synthesis a dual dopamine/5-HT1A receptor agonist MCL-135,which also exhibits a significant relief on LID while elicits its antiparkinsonian action.Conclusions 5-HT1A receptor plys an important role in the development of LID,targeted to dual dopamine/5-HT receptor may represent a promising strategy for drug design and discovery in LID and TD treatment.     

Cognitive functions in chronic schizophrenic patients with tardive dyskinesia

Two groups of chronic stable schizophrenics matched on several parameters but differing only with respect to presence or absence of tardive dyskinesia (TD) were compared for cognitive function using the Bexley Maudsley Automated Psychological Screen and the Category Sorting Test. The results showed that although all schizophrenics performed poorly on the psychometric tests in this inventory, there was no difference between the two groups for any of the cognitive functions tested. Stepwise multiple regression analysis performed on patients with TD revealed that age and extrapyramidal symptom (EPS) score were the only variables consistently associated with oro-facial TD where as EPS correlated inversely with TD of limbs and trunk. Our results did not support the hypothesis that tardive dyskinesia in schizophrenic patients is associated with additional or specific cognitive dysfunction.     

Valbenazine as the first and only approved treatment for adults with tardive dyskinesia

Introduction: Valbenazine is a selective VMAT2 inhibitor that the FDA approved in April 2017 for the specific treatment of tardive dyskinesia (TD), a movement disorder commonly caused by dopamine blocking agents. Valbenazine acts to decrease dopamine release, reducing excessive movement found in TD.

Areas covered: This drug profile reviews the development of valbenazine and the clinical trials that led to its approval as the first treatment specific to TD. The literature search was performed with the PubMed online database.

Expert commentary: Two clinical trials assessing the efficacy of valbenazine have shown the reduction of antipsychotic-induced involuntary movement. No life threatening adverse effects were found. Data from a 42-week extension study demonstrated sustained response.     

The association between risk factors for tardive dyskinesia and phenylalanine-induced abnormal movements in schizophrenia

We examined whether an oral challenge dose of the amino acid phenylalanine (a dopamine precursor) exacerbates the abnormal movements of tardive dyskinesia (TD). We also examined age, gender, treatment duration, and baseline movement severity in relation to phenylalanine-induced changes in movements. Lastly, we assessed the influence of fasting amino acid levels on phenylalanine-induced movements. In a placebo-controlled fashion, the abnormal involuntary movement scale (AIMS) was obtained on 25 patients before and after a phenylalanine challenge drink. A general linear model determined the relative effects of age, gender, treatment duration, and fasting amino acid levels on the magnitude of induced movements. Age and treatment duration did not affect phenylalanine-induced movements. Lower fasting levels of phenylalanine were associated with greater movements after controlling for age, F = 11.89, p < 0.003. The severity of abnormal movements at baseline also predicted response to phenylalanine, F = 8.62, p = 0.0079. Brain amino acid and neurotransmitter pools are influenced by changes in dietary protein, which may have implications in the development and prevention of movement disorders. This study suggests that fasting amino acid levels may predict differences in vulnerability to movements during an influx of neurotransmitter precursors, perhaps due to long-term compensatory changes in receptor sensitivity. Copyright 2001 John Wiley & Sons, Ltd.     

Pharmacotherapy for the treatment of tardive dyskinesia in schizophrenia patients

Introduction: Tardive dyskinesia (TD) is an iatrogenic movement disorder most commonly observed in patients with psychotic disorders who are treated with dopamine blocking antipsychotic medications. Treatment options are limited, and recommendations for treatment are based on a relative scarcity of evidence.

Areas covered: After briefly highlighting current mechanistic theories of TD, this review will discuss the evidence for a number of medications of several different classes that have been studied for the treatment of TD since the 1970s with an emphasis on placebo controlled trials when possible. We used a Pubmed search of primary studies, reviews, and metaanalyses on the topic of TD treatment in order to cover this topic.

Expert opinion: Treatment of TD is difficult given limited data and incomplete understanding of the mechanism. Treatment of TD must be evaluated on an individual basis with careful weight given to severity of symptoms. We suggest the use of atypical versus conventional antipsychotics whenever possible and would recommend trials with one or more of a number of additional agents starting with valbenazine.